{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T14:29:02Z","timestamp":1753885742511,"version":"3.41.2"},"reference-count":0,"publisher":"American Physiological Society","funder":[{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL147403"],"award-info":[{"award-number":["HL147403"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"abstract":"<jats:p> This study explored the role of apoE receptor-2 (apoER2), a unique member of the LDL receptor family proteins with a restricted tissue expression profile, in modulating diet-induced obesity and diabetes. Unlike wild type mice and humans in which chronic feeding of a high fat Western type diet leads to obesity and the pre-diabetic state of hyperinsulinemia prior to hyperglycemia onset, the Lrp8<jats:sup>-\/-<\/jats:sup> mice with global apoER2 deficiency displayed lower body weight and adiposity, slower development of hyperinsulinemia, but accelerated onset of hyperglycemia. Despite their lower adiposity, adipose tissues in Western diet-fed Lrp8<jats:sup>-\/-<\/jats:sup> mice were more inflamed compared to wild type mice. Additional experiments revealed that the hyperglycemia observed in Western diet-fed Lrp8<jats:sup>-\/-<\/jats:sup> mice was due to impaired glucose-induced insulin secretion, ultimately leading to hyperglycemia, adipocyte dysfunction, and inflammation upon chronic feeding of the Western diet. Interestingly, bone marrow-specific apoER2 deficient mice were not defective in insulin secretion, exhibiting increased adiposity and hyperinsulinemia compared to wild type mice. Analysis of bone marrow-derived macrophages revealed that apoER2 deficiency impeded inflammation resolution with lower secretion of IFN-\u03b2 and IL-10 in response to LPS stimulation of IL-4 primed cells. The apoER2-deficient macrophages also showed increased level of disabled-2 (Dab-2) as well as increased cell surface TLR4, suggesting that apoER2 participates in Dab-2 regulation of TLR4 signaling. Taken together, these results showed that apoER2 deficiency in macrophages sustains diet-induced tissue inflammation and accelerates obesity and diabetes onset while apoER2 deficiency in other cell types contributes to hyperglycemia and inflammation via defective insulin secretion. <\/jats:p>","DOI":"10.1152\/ajpregu.00007.2023","type":"journal-article","created":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T12:52:18Z","timestamp":1684759938000},"update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Different sensitivity to diet-induced hyperinsulinemia and hyperglycemia between mice with global or bone marrow-specific apoE receptor-2 deficiency"],"prefix":"10.1152","author":[{"given":"Patrick R.","family":"Wolfkiel","sequence":"first","affiliation":[{"name":"Molecular Genetics, Biochemistry, and Microbiology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"April M.","family":"Haller","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory  Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jillian","family":"Kirby","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory  Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja","family":"Jaeschke","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory  Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David Y.","family":"Hui","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory  Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","published-online":{"date-parts":[[2023,5,22]]},"container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.physiology.org\/doi\/pdf\/10.1152\/ajpregu.00007.2023","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,22]],"date-time":"2023-05-22T12:52:28Z","timestamp":1684759948000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.physiology.org\/doi\/10.1152\/ajpregu.00007.2023"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,22]]},"references-count":0,"alternative-id":["10.1152\/ajpregu.00007.2023"],"URL":"https:\/\/doi.org\/10.1152\/ajpregu.00007.2023","relation":{},"ISSN":["0363-6119","1522-1490"],"issn-type":[{"type":"print","value":"0363-6119"},{"type":"electronic","value":"1522-1490"}],"subject":[],"published":{"date-parts":[[2023,5,22]]},"assertion":[{"value":"2023-01-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"ajpregu.00007.2023"}}